ENDOTOXIN INDUCES CARDIAC HSP70 AND RESISTANCE TO ENDOTOXEMIC MYOCARDIAL DEPRESSION IN RATS

Endotoxin (bacterial lipopolysaccharide, LPS) depresses myocardial fun ction. However, heat shock and sublethal LPS can confer cardiac resist ance to postischemic dysfunction. We hypothesized that a prior exposur e to LPS stress induces the expression of cardiac heat shock protein 7 0 (HSP70) and resistance to endotoxemic myocardial depression. Moreove r, induction of HSP70 by hyperthermia should also increase cardiac res istance to LPS toxicity. LPS (500 mu g/kg ip) depressed rat left ventr icular developed pressure (LVDP) maximally at 6 h (58.4 +/- 3.72 vs. 1 01 +/- 1.46 mmHg in saline control, P < 0.01), and myocardial contract ile function recovered at 24 h. In rats pretreated with LPS 24 h earli er, subsequent LPS exposure did not depress LVDP (97.0 +/- 3.53 mmHg a t 6 h, P < 0.01 vs. single exposure). Both LPS and hyperthermia (42 de grees C, 15 min) induced HSP72 mainly in the cardiac interstitial cell s, including macrophages at 24 h after treatment. When hyperthermia-pr etreated animals were similarly challenged with LPS, myocardial depres sion at 6 h was partially abrogated (LVDP 80.1 +/- 5.67 vs. 62.2 +/- 4 .91 mmHg in sham + LPS group, P < 0.01). We conclude that LPS induces HSP70 in rat heart and that an exposure to LPS or heat stress confers cardiac resistance to endotoxemic myocardial depression.